The long-term objectives of this application are to maintain or improve the efficacy ofHodgkin's disease (HD) therapy while reducing late effects through a series of clinical trials in which novel, abbreviated chemotherapy is combined with reduced volumes and doses of radiation therapy. The specific aims in this proposal represent the evolution of prospective clinical trials conducted at Stanford University Medical Center continuously since 1962. During that period of time, the influence of advances in diagnostics, staging, multi-modality therapeutics and appreciation of the late effects of treatment has extended from HD management to that of other neoplasms. Although the cure rate of HD is high relative to other cancers, morbidity and mortality in excess of that expected on the basis of age and gender, primarily due to second cancers and ischemic heart disease provides a strong rationale for continued clinical investigations. In Aim 1, a risk-adapted Phase II trial is proposed for favorable, early stage disease in which patients will receive 12 weeks of chemotherapy alone or 8 weeks of chemotherapy and low dose radiotherapy. Following the success of Stanford V chemotherapy with or without radiotherapy and international consensus in prognostic factors in advanced HD, a Phase III Intergroup trial comparing this approach with ABVD is proposed in patients with 0-2 risk factors in Aim 2. For higher risk patients, those with 3 or more adverse factors, a Phase II trial of a novel chemotherapy regimen based upon Stanford V and introducing the new active agents, gemcitabine and vinorelbine, is planned in Aim 3. Aim 4 relates to the continued follow-up of patients enrolled in HD clinical trials at Stanford since 1962 and the provision of information management and statistical support to analyze efficacy and long-term morbidity and mortality. The ability to chronicle the late effects of treatment at Stanford has been made possible by a dedicated group of investigators, use of standardized diagnostics and treatments, and maintenance of a database now containing information on more than 3000 HD patients. Identification and notification of patients at risk is important for follow-up care and screening, where appropriate. Continued follow-up of HD patients and maintenance of the Stanford HD database, which can be considered a national resource, has never been more important as the time period after treatment of patients receiving lower doses and volumes of radiotherapy as well as novel combinations of chemotherapy approaches 10-15 years, a critical latency for second cancers.